Premature birth remains a significant health concern and an increasing proportion of very low birth weight infants are surviving. As a consequence, neonatologists are facing an expanding population of infants with poorly-understood diseases in whom prematurity is a major causative factor. Preterm delivery may expose genetic and epigenetic susceptibility to the extraordinary demands of adaptation to the environment of the nursery. New insights, based on modern genetic analysis are required to address this important problem area. Few physician-scientists or biomedical investigators are trained to understand the complex interplay between genes and environment in the immature host. The overall objective of the proposed Genes and Environment in Neonatal Education (GENE) Training Program is to provide research training for clinical and basic science investigators in the design, implementation and analysis of genome-wide genetic and epigenetic studies in neonates. The program is designed to integrate basic genetic training with research skills fundamental to the unique demands of genome-wide investigation. Using a two-mentor model in which a genetics or epigenetics mentor assists the trainee in understanding the application of modern state-of-the- art tools, while a mentor focused on biological problems in the neonate guides the trainee through clinical or developmental analyses specifically geared to understanding diseases in the NICU. A team of experts in genetics, epigenetics, and clinical/translational research has been assembled to facilitate this training effort. These mentors, combined with the outstanding clinical facilities and research cores of the Children's Hospital of Philadelphia, the University of Pennsylvania, the and the Stokes Research Institute will enhance the training experience of MD and PhD post-doctoral fellows and prepare them to become experts in this emerging field of research. PUBLIC HEALTH RELEVANCE: An increasing number of very premature infants are surviving with complex medical problems, reflecting the influence of environmental factors such as prematurity itself or transition to breathing and feeding on a genetically-susceptible neonate. Few scientists are trained to understand the interactions between genes and the unique environment of the premature infant. This training program attempts to correct that deficiency.